NITRO

The trial shows that the combination of durvalumab and standard chemotherapy was safe and has promising effects against mesothelioma. Tumour imaging by CT showed that 31 of 54 patients (57%) were alive and progression free at 6 months, which was higher than the expected outcomes with chemotherapy alone. The combination of durvalumab, cisplatin and pemetrexed showed promising activity and an accepted safety profile.

The use of circulating tumour DNA as liquid biopsies in cancer care is rapidly expanding.  ctDNA has many potential advantages as it is non-invasive and potentially more efficient and less-costly compared to tissue genotyping.  Accurate genotyping of lung cancer is of particular interest in the Australia/NZ due to high rates of targetable mutations in cancers, especially in the Māori and Pacific population^{1, 2}.  Furthermore, this technology can improve diagnostic and cancer monitoring in rural communities, where access to hospital-based services can be limited.  Data on the current usage and barriers to implementation is needed to support its use in clinical practice. This study aims to survey assess the current usage of ctDNA in clinical practice and identify barriers to implementation in the Australia/NZ.

Currently the standard of care in unresectable stage III NSCLC is concurrent chemoradiotherapy followed by consolidation durvalumab. This is regardless of the patient’s PD-L1 expression or oncogenic driver mutation status. This descriptive study employing a survey of current practices aims to determine patterns of Durvalumab prescribing in Australia in patients with stage IIIB unresectable non-small cell lung cancer. The ultimate goal is to aid in standardising cancer care in Australia

There are no available population-level clinical or patient-reported outcomes or treatment data for people living with mesothelioma in Victoria (or Australia). We do not know how many people are offered immunotherapy or other active treatments, nor do we have any insights into patient outcomes or their experiences of care. This research is designed to address this critically important unmet need. Aim: To understand patterns of care and the use of immunotherapy in patients with malignant mesothelioma (MM). Furthermore, the study aims to collect the patient-reported experience of care and their quality of life to inform a learning health system model to drive patient-centred improvements in quality of care.

Approximately one third of lung adenocarcinomas are driven by mutations in the oncogene Kirsten Rat Sarcoma Virus (KRAS). Immunotherapy has improved survival outcomes compared with standard chemotherapy both as a monotherapy, and in combination with chemotherapy. Approximately 20% of KRAS mutant lung cancers do not respond to immunotherapy due to co-occurring mutations in other genes. To enhance response to immunotherapy, combination treatments tailored for these tumours are needed. This research project aims to test whether using drugs specifically tailored to inhibit KRAS, in combination with immunotherapy in a laboratory setting, will provide evidence to suggest this approach is further assessed through clinical trials. This study also aims to identify novel drug targets to increase treatment options, and has the potential to identify new treatment regimens for improved survival in high-risk lung cancer patients.

The PEARL study examined whether early referral for palliative care improved quality of life, cost effectiveness and quality of end-of-life care for adults who were newly diagnosed with an advanced thoracic cancer. Participants were randomly allocated (by chance) to receive either standard care referral to palliative care at the discretion of the treating oncologist, or to receive early referral to palliative care within 7 days of enrolling in this clinical trial. With the exception of the timing of the referral, the palliative care received by each group was as per standard care, with information and care provided by the palliative care team as required for each participant. Participants were asked to complete a number of questionnaires relating to quality of life and cancer symptoms at regular time points. Carers were asked to complete quality of life and death questionnaires and an interview at regular intervals.

14/001 BR.31 examined whether durvalumab after surgery (and possibly chemotherapy) for Stage IB-IIIA PDL1-positive NSCLC prolonged disease-free survival. This type of treatment after surgery is known as adjuvant immunotherapy (or chemoimmunotherapy) treatment. Participants were randomly allocated (2:1 randomisation) to receive either durvalumab or placebo and followed up for a maximum of 10 years to assess overall survival and disease-free survival.

BR.34 compared the overall survival following an immunotherapy treatment combination of both durvalumab plus tremelimumab with or without chemotherapy in metastatic NSCLC. Participants were allocated by chance to one of two treatment groups. Participants in both groups received durvalumab and tremelimumab every 28 days for 4 cycles followed by durvalumab every 28 days until disease progression. Participants in one group only also received one of two types of chemotherapy during durvalumab and tremelimumab treatment. Patients with squamous cell NSCLC received gemcitabine and cisplatin or carboplatin chemotherapy, and patients with non-squamous NSCLC received pemetrexed and cisplatin or carboplatin chemotherapy.

The NIVORAD trial was a randomised phase II study evaluating whether adding stereotactic ablative body radiotherapy (SABR) to nivolumab improves outcomes in patients with metastatic, immunotherapy-naïve non-small cell lung cancer (NSCLC) that had progressed after chemotherapy. Patients were randomised to receive nivolumab alone or nivolumab plus a single fraction of SABR to one metastatic site early in treatment. Key Findings: At a median follow-up of approximately two years, the addition of SABR to nivolumab did not significantly improve progression-free survival compared with nivolumab alone. Six-month PFS was similar between groups (49 % with SABR vs 44 % with nivolumab alone), and the hazard ratio suggested no statistically significant difference (HR 0.68; p = 0.23). Objective tumour response rates were comparable (about 24–25 %), and overall survival did not differ meaningfully between the treatment arms (HR 0.86; p = 0.69). Rates of serious adverse events (Grade 3–5) were also similar, and there was no apparent increase in toxicity with the addition of SABR. Overall, nivolumab plus single-fraction SABR exhibited similar efficacy and safety to nivolumab alone in this patient population.

STIMULI investigated the efficacy and tolerability of the standard treatment (chemotherapy and radiotherapy) alone, compared with the standard treatment followed by nivolumab and ipilimumab (immunotherapy) in patients with limited stage SCLC. The results of STIMULI showed no significant difference between the immunotherapy and observation groups. Overall, there was no difference in the percentage of people with cancer progression at 12 and 24 months after starting immunotherapy or observation. There was also no difference in the percentage of people alive at 24 months, and the amount of tumour shrinkage was no different between the two groups. There was some data to suggest that immunotherapy after a more frequent radiotherapy schedule may be more effective, but this needs to be studied further.

OSCILLATE measured the duration before progression when patients with EGFR-T790 mutation positive advanced NSCLC were treated with osimertinib and gefitinib. It was hypothesised that alternating therapy with the gefitinib and osimertinib would modulate the populations of EGFR-T790M positive and negative tumour clones, delaying the emergence of resistance to osimertinib. Sixty-eight percent of participants in OSCILLATE were able to complete 6 months of treatment without any delays or interruptions due to side effects, suggesting that the alternating approach was safe and feasible. The lung cancer was still under control 12 months after starting treatment in 38% of the participants, but this was not a statistically significant outcome. The side effects of treatment in OSCILLATE were similar to those seen in trials using either drug on its own. Accompanying translational research studies on samples obtained from patients have contributed to current understanding of resistance to EGFR tyrosine kinase inhibitor therapy.

ILLUMINATE evaluated the efficacy and tolerability of immunotherapy (durvalumab and tremelimumab) with platinum-pemetrexed chemotherapy in patients with metastatic EGFR-mutant NSCLC (T790M+ve or T790M-ve) who had progressed following prior EGFR TKI therapy. At the time the ILLUMINATE study commenced, the role of immunotherapy for patients with EGFR+ NSCLC that had progressed on a third generation TKI was unclear. Various studies suggested benefit, but differed in whether immunotherapy was delivered as monotherapy, as a dual immunotherapy combination or together with chemotherapy.

The primary purpose of the ALKTERNATE clinical trial was to evaluate the efficacy, safety and feasibility of alternating lorlatinib and crizotinib for the treatment of ALK-rearranged advanced NSCLC, and to provide information on the potential to delay the emergence of drug resistance as compared to continuous lorlatinib therapy alone. The study found that alternating crizotinib and lorlatinib could be done safely and did not compromise the control of cancer compared to usual care. However, since the trial commenced, lorlatinib has become first line standard of care therapy for ALK+ NSCLC. Blood samples collected from patients during treatment on the ALKTERNATE clinical trial revealed that every ALK+ NSCLC patient is different, with no one clear mechanism identified for resistance to treatment.